Distinctive pathologic findings in proximal diabetic neuropathy (diabetic amyotrophy)

Objective: To investigate the pathogenesis of proximal diabetic neuropathy (PDN) with nerve and muscle biopsies. Background: Recent evidence suggests that nerve ischemia secondary to immune-mediated vasculopathy rather than d iabetic microangiopathy may be responsible for PDN. Method: Fifteen patient s with PDN and two diabetic controls underwent nerve and muscle biopsy and clinical, electrophysiologic, and laboratory evaluation. There were eight m en and seven women between 49 and 79 years of age with type II diabetes. Al l had progressive, painful, asymmetric, proximal weakness with duration of 5 weeks to 12 months. None had evidence of systemic autoimmune disorder. Re sults: Four patients showed the distinctive findings of polymorphonuclear s mall-vessel vasculitis affecting epineurial vessels with transmural infiltr ation of postcapillary venules with polymorphonuclear leukocytes. Immunoglo bulin M (IgM) deposits were found along the endothelium and intramurally in affected vessels. IgM staining was seen in the subperineurial space and in the endoneurium. Activated complement deposition was seen along endotheliu m of small vessels. Three of these four patients were evaluated within 6 se eks of onset of PDN, and the fourth patient during acute flare of PDN 6 mon ths after the initial onset. Six patients showed "perivasculitis" with mono nuclear cell infiltrates around small epineurial vessels without vasculitis (fibrinoid necrosis or transmural inflammation). One patient showed recana lized vessels with transmural lymphocytes without fibrinoid necrosis, possi bly suggesting healed vasculitis. Conclusion: These distinctive pathologic findings support that proximal diabetic neuropathy has an immune-mediated i nflammatory basis and suggest that polymorphonuclear vasculitis with immune complex and complement deposition may be the primary event in the acute ph ase of proximal diabetic neuropathy.